We propose to continue a prospective study of HIV infection among intravenous drug users (IVDUs) to define the course of infection and factors that are associated with progression to immunosuppression and AIDS in IVDUs. Based upon our preliminary findings from the first four years of this study, we hypothesize that progression may occur more slowly in IVDUs than other risk groups, that females may progress faster than men, and that IVDUs present with HIV-related non-AIDS diseases. Data to be collected provide a valuable source for evaluating to what extent interventions (e.g., chemotherapeutic, behavioral) modify the natural history of HIV infection in IVDUs. Factors associated with survival following diagnosis of AIDS need clarification. To study these and other issues, we propose to continue follow-up of a cohort of IVDUs established in 1988 and early 1989 (DA 04334). This cohort was identified by screening 2,921 IVDUs recruited through extensive community outreach; 630 HIV seropositive and 160 seronegatives were enrolled for detailed semiannual follow-up; we have also identified 105 HIV seroconverters who have been entered into follow-up. We propose to continue this follow-up of the 895 IVDUs with semiannual visits to obtain detailed interviews on medical conditions, drug use and sexual activity; a physical exam; and phlebotomy for immunologic studies including measurement T-cell subsets and storage of cells and serum for future studies. Diagnosis of AIDS as well as non-AIDS related conditions, is documented with medical record review. Longitudinal data and survival analyses procedures, and logistic regression techniques for nested case-control studies will be used. Continuation will provide a cumulative total of 7 years of follow-up; thus permitting important questions on progression, risk factors, and survival in IVDUs and comparisons to other risk groups can be clarified and addressed.